Objective To explore the mechanism of lncRNA-BC200 (BC200) targeting the ubiquitination of Beta-site APP cleaving enzyme 1 (BACE1) and regulating the repair of nerve cell injury. Methods Mouse hippocampal neuron cell line HT22 was divided into four groups: control group, oxygen-glucose deprivation/reoxygenation(OGD/R) group, OGD/R+si-NC group and OGD/R+si-BC200 group. In order to further explore the relationship between BC200 and BACE1, HT22 cells were divided into four groups: OGD/R group, OGD/R+si-BC200 group, OGD/R+si-BC200+NC group and OGD/R+si-BC200+ BACE1 group. Twenty male C57BL/6J mice were randomly assigned to the following four groups: control group, middle cerebral artery occlusion (MCAO) group, MCAO+si-BC200 group and MCAO+si-BC200+BACE1 group. The mRNA expression levels of BC200 and BACE1 in cells were measured by real-time quantitative reverse transcription polymerase chain reaction. The expressions of c-caspase-3, B-cell lymphoma 2 (Bcl2), Bcl2 associated X protein(BAX) and BACE1 were detected by western blot, and the apoptotic cells were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. Results Compared with the control group, the activity of HT22 cells in OGD/R group decreased significantly, and the percentage of apoptotic cells increased significantly. Compared with OGD/R+si-NC group, the activity of HT22 cells in OGD/R+si-BC200 group increased significantly, and the percentage of apoptotic cells decreased significantly. Compared with the control group, the expression of BACE1 protein in HT22 cells in OGD/R group was significantly enhanced. Compared with OGD/R+si-NC group, the expression of BACE1 protein in HT22 cells in OGD/R+si-BC200 group decreased significantly. It was observed that after OGD/R treatment, the ubiquitination level of BACE1 decreased significantly and the expression of BACE1 protein increased significantly. After transfection with si-BC200, the ubiquitination level of BACE1 protein increased significantly, while the expression of BACE1 protein decreased significantly. Compared with OGD/R+si-BC200+NC group, the percentage of apoptotic cells, the expression of c-caspase-3 and Bax protein in HT22 cells in OGD/R+si-BC200+BACE1 group increased significantly, and the expression of Bcl2 protein decreased significantly. Compared with the control group, the number of cerebral infarction areas and TUNEL positive cells in MCAO group increased significantly, and the survival number of neurons decreased significantly. Compared with the MCAO group, the number of cerebral infarction areas and TUNEL positive cells in MCAO+si-BC200 group decreased significantly, and the survival number of neurons increased significantly, while the addition of BACE1 reversed the improvement of si-BC200 transfection. Conclusion The combination of BC200 and BACE1 inhibit the ubiquitination of BACE1, and participate in mediating the expression enhancement of BACE1 induced by OGD/R. Specific blocking of BC200/BACE1 axis may be a potential therapeutic target to protect neurons from apoptosis induced by cerebral ischemia/reperfusion.
Animals ; Amyloid Precursor Protein Secretases/genetics* ; RNA, Long Noncoding/physiology* ; Aspartic Acid Endopeptidases/genetics* ; Male ; Neurons/pathology* ; Mice ; Mice, Inbred C57BL ; Apoptosis/genetics* ; Ubiquitination ; Cell Line ; Hippocampus/metabolism* ; bcl-2-Associated X Protein/genetics* ; Caspase 3/genetics* ; Infarction, Middle Cerebral Artery/metabolism*

Adult ; Cerebral Infarction ; diagnosis ; diagnostic imaging ; etiology ; Heart Atria ; diagnostic imaging ; pathology ; Humans ; Magnetic Resonance Imaging ; Male ; Myxoma ; complications ; diagnostic imaging

Cerebral Infarction ; complications ; Cerebral Veins ; pathology ; Humans ; Thrombosis ; Venous Thrombosis ; etiology

Astrocytes are the most abundant cells in the central nervous system and play significant roles in normal brain. With cerebral infarction, astrocytes are activated as reactive astrocytes and form glial scars, which play an essential part in brain injury. According to their roles in neuroprotection after cerebral infarction, regulation of scar formation, nerve regeneration, maintenance of blood-brain barrier, promotion of angiogenesis and immune response, scholars have proposed a variety of therapeutic strategies based on targeting astrocytes. This article reviews the research progress on the changes in astrocyte signaling pathways before and after cerebral infarction and the related therapeutic strategies.
Astrocytes ; Cerebral Infarction ; physiopathology ; therapy ; Humans ; Neuroglia ; pathology ; Signal Transduction

Acupuncture Therapy ; Aged ; Aneurysm, Dissecting ; complications ; Brain ; diagnostic imaging ; pathology ; Cerebral Infarction ; etiology ; therapy ; Female ; Glasgow Coma Scale ; Humans ; Postoperative Complications ; etiology ; therapy ; Tomography, X-Ray Computed

Brain ; pathology ; Brain Infarction ; diagnosis ; Cerebral Angiography ; Cerebral Arterial Diseases ; diagnosis ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Posterior Cerebral Artery ; pathology

BACKGROUNDCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small artery disease caused by NOTCH3 gene mutation. We performed enhanced depth imaging optical coherence tomography (EDI-OCT) to evaluate the retinal vessel changes in CADASIL patients and assessed their consonance with brain magnetic resonance imaging (MRI) findings.

METHODSOf 27 genetically confirmed patients and an equal number of controls were recruited at the Peking University First Hospital from January 2015 to August 2016. All patients underwent 7T-MRI of the brain. Fazekas score, number of small infarcts and microbleeds were evaluated. All patients and controls underwent EDI-OCT to measure subfoveal choroidal thickness (SFCT), inner and outer diameters as well as arterial and venous wall thickness, and arterial venous ratio of the inner (AVRin) and outer diameters (AVRout). The relation between retinal vessel changes and Fazekas scores, numbers of small infarcts, or microbleeds was analyzed. Paired t-test was used to compare the SFCT and retinal vessel measurement data between patients and controls. Spearman's correlation was used to investigate the correlation between retinal vessel changes and MRI lesions.

RESULTSIn CADASIL patients, mean SFCT (268.37 ± 46.50 μm) and mean arterial inner diameter (93.46 ± 9.70 μm) were significantly lower than that in controls (P < 0.001,P = 0.048, respectively). Mean arterial outer diameter (131.74 ± 10.87 μm), venous inner (128.99 ± 13.62 μm) and outer diameter (164.82 ± 14.77 μm), and mean arterial (19.13 ± 1.85 μm) and venous (17.91 ± 2.76 μm) wall thickness were significantly higher than that in controls (P = 0.023,P = 0.004,P < 0.001,P < 0.001, respectively). Arterial inner diameter (rs= -0.39, P= 0.044), AVRin (rs= -0.65,P < 0.001), and AVRout (rs= -0.56, P= 0.002) showed a negative correlation with the number of small infarcts. Venous inner diameter (rs = 0.46, P= 0.016) showed a positive correlation with the number of small infarcts. Venous inner diameter (rs = 0.59, P= 0.002), outer diameter (rs = 0.47, P= 0.017), showed a positive correlation with the number of cerebral microbleeds (CMBs). AVRin (rs= -0.52, P= 0.007) and AVRout (rs= -0.40, P= 0.048) showed a negative correlation with the number of CMBs.

CONCLUSIONSMeasurement of retinal vessels using EDI-OCT correlates moderately well with MRI parameters. EDI-OCT might be a useful evaluation tool for CADASIL patients.

Adult ; Brain ; metabolism ; CADASIL ; Cerebral Infarction ; pathology ; Female ; Humans ; Leukoencephalopathies ; pathology ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Mutation ; Receptor, Notch3 ; genetics ; Retinal Vessels ; metabolism ; Tomography, Optical Coherence ; methods

Intracranial hemorrhage is common and is caused by diverse pathology, including trauma, hypertension, cerebral amyloid angiopathy, hemorrhagic conversion of ischemic infarction, cerebral aneurysms, cerebral arteriovenous malformations, dural arteriovenous fistula, vasculitis, and venous sinus thrombosis, among other causes. Neuroimaging is essential for the treating physician to identify the cause of hemorrhage and to understand the location and severity of hemorrhage, the risk of impending cerebral injury, and to guide often emergent patient treatment. We review CT and MRI evaluation of intracranial hemorrhage with the goal of providing a broad overview of the diverse causes and varied appearances of intracranial hemorrhage.
Arteriovenous Malformations ; Central Nervous System Vascular Malformations ; Cerebral Amyloid Angiopathy ; Cerebral Infarction ; Craniocerebral Trauma ; Hematoma, Subdural ; Hemorrhage ; Humans ; Hypertension ; Intracranial Aneurysm ; Intracranial Hemorrhages* ; Magnetic Resonance Imaging ; Neuroimaging ; Pathology ; Sinus Thrombosis, Intracranial ; Subarachnoid Hemorrhage ; Vasculitis

PURPOSE: Patients with superficial middle cerebral artery (MCA) territory infarction may have concomitant lenticulostriate artery (LSA) territory infarction. We investigated the mechanisms thereof and the outcomes of patients with superficial MCA territory infarction according to the presence or absence of LSA involvement. MATERIALS AND METHODS: Consecutive patients with first-ever infarction in the unilateral superficial MCA territory were included in this study. They were divided into the superficial MCA only (SM) group and the superficial MCA plus LSA (SM+L) group. RESULTS: Of the 398 patients, 84 patients (21.1%) had LSA involvement (SM+L group). The SM+L group more frequently had significant stenosis of the proximal MCA or carotid artery and high-risk cardioembolic sources. Stroke severity and outcomes were remarkably different between the groups. The SM+L group showed more severe neurologic deficits (National Institute of Health Stroke Scale score 10.8±7.1 vs. 4.0±5.0, p<0.001) and larger infarct in the superficial MCA territory (40.8±62.6 cm³ vs. 10.8±21.8 cm³, p<0.001) than the SM group. A poor functional outcome (mRS >2) at 3 months was more common in the SM+L group (64.3% vs. 15.9%, p<0.001). During a mean follow-up of 26 months, 67 patients died. All-cause (hazard ratio, 2.246) and stroke (hazard ratio, 9.193) mortalities were higher in the SM+L group than the SM group. In multivariate analyses, LSA involvement was an independent predictor of poor functional outcomes and stroke mortality. CONCLUSION: LSA territory involvement is predictive of poor long-term outcomes in patients with superficial MCA territory infarction.
Carotid Stenosis/mortality/pathology ; Constriction, Pathologic/pathology ; Female ; Humans ; Infarction, Middle Cerebral Artery/mortality/*pathology ; Male ; Middle Cerebral Artery/*pathology ; Multivariate Analysis ; Severity of Illness Index ; Stroke/mortality/pathology

OBJECTIVETo explore the neuroprotective effect and mechanism of picroside II on extracellular regulated protein kinases1/2 (ERK1/2) signal transduction pathway in cerebral ischemia injuryrats. METHODS The middle cerebral artery occlusion (MCAO) model was established by inserting a monofilament into middle cerebral artery. Totally 96 successfully modeled Wistar rats were divided into the modelgroup, the treatment (picroside II) group, the Lipopolysachcaride (LPS) group, and the U0126 group according to random digit table. Each group was further divided into 3 subgroups, i.e. 6, 12, and 24 h sub-groups. Picroside II (20 mg/kg) was peritoneally injected to rats in the treatment group 2 h after ischemia.LPS (20 mg/kg) and Picroside II (20 mg/kg) were peritoneally injected to rats in the LPS group 2 h after ischemia. U0126-EtOH (20 mg/kg)and Picroside II (20 mg/kg) were peritoneally injected to rats in the U0126group 2 h after ischemia. Equal volume of normal saline was peritoneally injected to rats in the control groupand the model group. The neurobehavioral function was evaluated by modified neurological severity score(mNSS) test. The structure of neurons was observed using hematoxylin-eosinstaining (HE) staining. Theapoptotic cells were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expression of phosphorylated extracellular signal-regulated protein kinase1,2 (pERK1,2) in cortex was detected using immunohistochemistry (IHC) and Western blot.

RESULTSAfter cerebral ischemia injury neurological impairment score increased, the damage of neuron in the cortical area was aggravated, apoptotic cells increased in the model group as time went by. The expression of pERK1/2 increased more significantly in the model group than in the control group (P <0.05). The damage of neuron in the cortical area was milder, while apoptotic cells decreased, the expression of pERK1f2 obviously decreased more in the treatment group and the U0126 group (P < 0.05). The early damage of neuron in the cortical area was more severe, apoptotic cells and the expression of pERK12 were comparatively higher in early stage of the LPS group, but the expression of pERK1/2 was somewhat decreased in late stage.

CONCLUSIONSActivating ERK12 pathway could mediate apoptosis and inflammatory reactions of neurons after cerebral ischemia injury. Picroside II could protect the nerve system possibly through reducing activation of ERKI2 pathway, inhibiting apoptosis of neurons and inflammation reaction.

Animals ; Apoptosis ; Brain Ischemia ; drug therapy ; Cinnamates ; pharmacology ; Infarction, Middle Cerebral Artery ; drug therapy ; Iridoid Glucosides ; pharmacology ; MAP Kinase Signaling System ; drug effects ; Neurons ; pathology ; Neuroprotective Agents ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar